ABSTRACT/SUMMARY In previous studies we identified novel non-hematopoietic umbilical cord blood stem cells (nh- UCBSCs) that could be expanded to high passages and exhibit restorative properties following ischemic brain injury repair. We found that the high passaged cells were equivalent, if not even better, than the low passaged nh-UCBSCs. This finding suggests that these cells can serve as a source of highly expandable cells that can be manufactured under controlled conditions for potential therapeutic applications. In this Phase I/II proposal we intend to scale-up production of nh-UCBSCs under good manufacturing practice (GMP) conditions at the GMP facility located on the campus of the University of Minnesota. These GMP manufactured cells will then be tested for efficacy using small animal (laboratory rat) and large animal (non-human primate) models of ischemic brain injury. In consultation with the FDA we are proposing IND-enabling studies to further qualifying these cells for use in a future clinical study. We will evaluate the safety and potential tumorigenicity of these cells, evaluate mechanisms of action and effects of cryopreservation. The results from this study will provide key data required by the Food and Drug Administration for an IND to conduct a clinical trial on the use of these cells in the treatment of ischemic brain injury.